A new era of incorporation of fluorine atom on organic compounds: modern methods and use of 19f magnetic resonance spectroscopy

During the last decades, the incorporation of the fluorine atom in organic molecules suffered an increase, mainly in the pharmaceutical and agrochemical industries, due to the unique properties of the fluorine atom and the desired behaviour of the molecules resulting from fluorination processes. We present the rise and historical evolution of both fluorination agents, nucleophilic and electrophilic agents, and the three fluorination conditions, nucleophilic, electrophilic and neutral (radical) conditions. The advantages and disadvantages of each type of fluorination agent and condition are highlighted employing modern methods of fluorination, along with the presentation of the author's mechanistic proposals and discussion of the scope of the reaction. Green chemistry, more sustainable procedures and the use of alternative methods are gaining more attention and are the challenges of the fluorination of organic compounds. 19F NMR technique is also highlighted as a powerful tool for structural elucidation, intermediates identification and reaction monitoring. 1D and 2D NMR experiments involving fluorine are widely employed in biological areas and need to be more widespread in organic synthesis to help face the challenges of this area.